Jia Chen received her Sc.D. in 1994 in the fields of Toxicology and Environmental Engineering from Massachusetts Institute of Technology. Since 1995 she has been working as a Research Associate in Medicine at Harvard Medical School and a Research Fellow at Harvard School of Public Health. She is interested in an academic research career in molecular epidemiology studying genetic susceptibility to cancer. David J. Hunter, MBBS, MPH, ScD, has extensive experience in chronic disease and molecular epidemiology. He has mentored numerous graduate students and postdoctoral fellows; two graduate students he co- supervised are now postdoctoral fellows in the NCI Genetic Epidemiology Program. He is a co-investigator of the Nurses' Health Study I and Health Professionals Follow-Up Study based at Harvard. Dr. Hunter is familiar with the research methods proposed in this project and he will oversee Dr. Chen's research activities and education. Dr. Chen proposes to use the resources of three large well-characterized cohort studies (the Nurses' Health Study I, the Health Professionals Follow-Up Study, and the Physicians Health Study) to prospectively assess gene-nutrient and other gene-environment interactions in the etiology of colorectal adenoma and carcinoma. Specifically, she will assess whether polymorphisms in the alcohol dehydrogenase type 3 (ADH3), cytochrome P450IIE1 (CYP2E1), and methylenetetrahydrofolate reductase (MTHFR) genes are associated with these cancers and whether they modify associations with intake of folate, methionine and alcohol, as well as other potentially carcinogenic or anticarcinogenic nutrients on risk of colon cancer and polyps. In addition, she will modify the existing PCR- RFLP based genotyping methods and adapt more flexible and efficient technologies while maintaining high accuracy. The proposed study would be valuable as positive associations would clearly implicate the substrates of the gene product as environmental carcinogenic exposures, clarifying colon cancer etiology and pointing to preventive dietary and other lifestyle modifications.